HTLV-1 contains a high CG dinucleotide content and is susceptible to the host antiviral protein ZAP
| العنوان: | HTLV-1 contains a high CG dinucleotide content and is susceptible to the host antiviral protein ZAP |
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| المؤلفون: | Paola Miyazato, Saiful Islam, Benjy J. Y. Tan, Michiyo Tokunaga, Yorifumi Satou, Hiroo Katsuya, Jumpei Ito, Yasuhiro Murakawa, Misaki Matsuo |
| المصدر: | Retrovirology, Vol 16, Iss 1, Pp 1-11 (2019) Retrovirology |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | lcsh:Immunologic diseases. Allergy, viruses, ZAP, Antiviral protein, Viremia, Virus, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Retrovirus, Proviruses, Virology, Sense (molecular biology), Tropical spastic paraparesis, medicine, Humans, RNA Processing, Post-Transcriptional, RNA, Small Interfering, 030304 developmental biology, Human T-lymphotropic virus 1, 0303 health sciences, biology, Post-transcriptional regulation, Research, RNA-Binding Proteins, biology.organism_classification, medicine.disease, Cap analysis gene expression, Retroviral latency, Infectious Diseases, Gene Expression Regulation, HTLV-1, Gene Knockdown Techniques, biology.protein, HIV-1, Antibody, lcsh:RC581-607, Dinucleoside Phosphates, 030217 neurology & neurosurgery, HeLa Cells |
| الوصف: | Background Human T cell leukaemia virus type 1 (HTLV-1) is a retrovirus associated with human diseases such as adult T-cell leukaemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. In contrast to another human retrovirus, human immunodeficiency virus type 1 (HIV-1), HTLV-1 persists in the host not via vigorous virus production but mainly via proliferation and/or long-term survival in the form of silent proviruses in infected host cells. As a result, HTLV-1-infected cells rarely produce virus particles in vivo even without anti-retroviral treatment. That should be an advantage for the virus to escape from the host immune surveillance by minimizing the expression of viral antigens in host cells. However, why HIV-1 and HTLV-1 behave so differently during natural infection is not fully understood. Results We performed cap analysis of gene expression (CAGE) using total RNAs and nascent, chromatin-associated, RNAs in the nucleus and found that HTLV-1 RNAs were processed post-transcriptionally in infected cells. RNA processing was evident for the sense viral transcripts but not the anti-sense ones. We also found a higher proportion of CG di-nucleotides in proviral sequences of HTLV-1-infected cells, when compared to the HIV-1 genomic sequence. It has been reported recently that CG dinucleotide content of viral sequence is associated with susceptibility to the antiviral ZC3HAV1 (ZAP), suggesting the involvement of this protein in the regulation of HTLV-1 transcripts. To analyse the effect of ZAP on HTLV-1 transcripts, we over-expressed it in HTLV-1-infected cells. We found there was a dose-dependent reduction in virus production with ZAP expression. We further knocked down endogenous ZAP with two independent targeting siRNAs and observed a significant increase in virus production in the culture supernatant. Other delta-type retroviruses such as simian T-cell leukaemia virus and bovine leukaemia virus, also contain high CG-dinucleotide contents in their viral genomes, suggesting that ZAP-mediated suppression of viral transcripts might be a common feature of delta-type retroviruses, which cause minimal viremia in their natural hosts. Conclusions The post-transcriptional regulatory mechanism involving ZAP might allow HTLV-1 to maintain a delicate balance required for prolonged survival in infected individuals. |
| اللغة: | English |
| تدمد: | 1742-4690 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c483cd3fb4a1dce5cbd09034d52e367Test https://doaj.org/article/fcfb96766f324f098bceeab63e57303aTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8c483cd3fb4a1dce5cbd09034d52e367 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17424690 |
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